NDLI: Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase.

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Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bloom, F. E. Fox, H. S. Wagaman, P. C. Lerner, D. L. Phillips, T. R. Elder, J. H. Prospero-garcia, O. Henriksen, S. J.
Description	Author Affiliation: Lerner DL ( Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.);
Abstract	Feline immunodeficiency virus (FIV) encodes the enzyme deoxyuridine-triphosphatase (DU; EC 3.6.1.23) between the coding regions for reverse transcriptase and integrase in the pol gene. Here, we report the in vivo infection of cats with a DU- variant of the PPR strain of FIV and compare its growth properties and tissue distribution with those of wild-type FIV-PPR. The results reveal several important points: (i) DU- FIV is able to infect the cat, with kinetics similar to that observed with wild-type FIV; (ii) both wild-type and DU- FIV-infected specific-pathogen free cats mount a strong humoral antibody response which is able to limit the virus burden in both groups of animals; (iii) the virus burden is reduced in the DU- FIV-infected cats, particularly in tissues such as spleen and salivary gland; and (iv) the mutation frequency in DU- FIVs integrated in the DNA of primary macrophages after 9 months of infection is approximately 5-fold greater than the frequency observed in DU- FIV DNA integrated in T lymphocytes. Mutation rate with wild-type FIV remains the same in both cell types in vivo. The dominant mutations seen in macrophages with DU- FIV are G-->A base changes, consistent with an increased misincorporation of deoxyuridine into viral DNA of DU- FIVs during reverse transcription. Because this enzyme is absent from human immunodeficiency virus type 1 and other primate lentiviruses, virus replication in cell environments with low DU activity may lead to increased mutation and contribute to the rapid expansion of the viral repertoire.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Immunodeficiency Virus, Feline Enzymology Genetics Mutation Pyrophosphatases Amino Acid Sequence Animals Capsid Immunology DNA Primers DNA, Viral Feline Acquired Immunodeficiency Syndrome Virology Genes, Pol Genome, Viral Growth & Development Molecular Sequence Data Polymerase Chain Reaction Tissue Distribution Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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